Human milk oligosaccharides (HMOs) are carbohydrates which have gained much interest in recent years. In particular the synthesis of these HMOs has increased significantly due to the role of HMOs in numerous biological processes occurring in humans. HMOs play a vital role in the early development of young children. Furthermore, the importance of HMOs in the maturation of the immune system and their prognostic use as immunomodulators underlines their importance.
A natural source of such HMOs is mammalian milk. Mammalian milk contains up to 10% HMOs. To date the structure of at least 115 HMOs has been determined while the mass spectra (MS) data has suggested a presence of almost 130 HMOs (Newburg and Neubauer, 1995, Carbohydrates in milks: Analysis, quantities and significance. In: Handbook of Milk Composition (R. G. Jensen, ed.), pp. 273-249, Academic Press, San Diego, USA).
The 115 human milk oligosaccharides, the structures of which have been determined to date, can be grouped into 13 categories based on their core structures. Such 13 categories structures are exemplarily shown in table 1 below (see also Urashima et al., Advanced Dairy Chemistry, Volume 3: Lactose, Water, Salts and Minor Constituents, 2009, pp. 295-349; and TADASU URASHIMA et al, MILK OLIGOSACCHARIDES, Nova Biomedical Books, New York, 2011, ISBN: 978-1-61122-831-1).
TABLE 113 different core structures of human milk oligosaccharides (HMOs)NoAbbreviationCore structure1LactoseGal(β1-4)Glc2Lacto-N-tetraoseGal(β1-3)GlcNAc(β1-3)Gal(β1-4)Glc(LNT)3Lacto-N-Gal(β1-4)GlcNAc(b 1-3)Gal(β1-4)Glcneotetraose(LNnT) 4Lacto-N- hexaose (LNH) 5Lacto-N- neohexaose (LNnH) 6para-Lacto-N-Gal(β1-3)GlcNAc(β1-3)Gal(β1-4)GlcNAc(β1-hexaose3)Gal(β1-4)Glc(para-LNH))7para-Lacto-N-Gal(β1-4)GlcNAc(β1-3)Gal(β1-4)GlcNAc(β1-neohexaose3)Gal(β1-4)Glc(para-LNnH) 8Lacto-N- octaose (LNO) 9Lacto-N- neooctaose (LNnO) 10Iso-Lacto-N- octaose (iso-LNO) 11para-Lacto-N-Gal(β1-3)GlcNAc(β1-3)Gal(β1-4)GlcNAc(β1-octaose3)Gal(β1-4)GlcNAc(β1-3)Gal(β1-4)Glc(para-LNO) 12Lacto-N- decaose (LND) 13Lacto-N- neodecaose (LNnD)
Due to the large number of HMOs and their low concentrations in mammalian milk, an isolation of HMOs from mammalian milk is a difficult task. It is therefore difficult to provide suitable HMOs replacements in foods, particularly in infant formulae which display at least part of the entire spectrum of HMOs.
Although methods for the manufacture of HMOs are known, be it chemically or enzymatically, such manufacturing methods do not allow the preparation of mixtures of HMOs. Preparing such mixtures of HMOs on the basis of individually designed syntheses of single HMOs is furthermore costly and may not resemble the large variety of naturally occurring HMOs.
There is a need to provide a means for the manufacture of a mixture of HMOs wherein the mixture of HMOS has a profile which resembles a mixture of HMOs as found in human milk.
There is also a need to be able to provide a method for the manufacture of HMOs on a relatively large scale, which avoids the use of complicated and expensive methods such as those methods which utilises biotechnology.
There is a need to provide a method, which allows for the manufacture of a mixture of HMOs on a large scale.